Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes, proteins, and differentiated products as an approach to reducing to experimental dimensions human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of such essential products. Enzymes, proteins, and differentiated products will be studied that depend on several genes for their final expression and, when altered, result in abnormal development and severe inherited disease. The genetic dissection and chromosome mapping of genes necessary for the final realization of these products will be studied using normal and deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. A genetic dissection and chromosome mapping of molecular disorders using somatic cell hybrids will provide a better understanding of metabolic diseases which are often fatal and will determine what type of gene is abnormal and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.